C-Glucosylated malonitrile as a key intermediate towards carbohydrate-based glycogen phosphorylase inhibitors

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• 作者：Sophie Feuillastre ; Aikaterini S. Chajistamatiou ; Constantinos Potamitis ; Maria Zervou ; Panagiotis Zoumpoulakis ; Evangelia D. Chrysina ; Jean-Pierre Praly ; S¨¦bastien Vidal
• 关键词：Carbohydrate ; Glycogen phosphorylase ; 1 ; 3-Dipolar cycloaddition ; Malonitrile ; Pyrimidinone
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：15 September, 2012
• 年：2012
• 卷：20
• 期：18
• 页码：5592-5599
• 全文大小：705 K

文摘

Glycogen utilization involves glycogen phosphorylase, an enzyme which appears to be a potential target for the regulation of glycaemia, as the liver isoform is a major player for hepatic glucose output. A single C-glucosylated malonitrile allowed for the synthesis of three glucose-based derivatives namely bis-oxadiazoles, bis-amides and a C-glucosylated tetrahydropyrimidin-2-one. When evaluated as glycogen phosphorylase inhibitors, two of the synthesized compounds displayed inhibition in the sub-millimolar range. In silico studies revealed that only one out of the bis-amides obtained and the C-glucosylated tetrahydropyrimidin-2-one may bind at the catalytic site.